The implementation of CDK 4/6 inhibitors and its impact on treatment choices in HR+/HER2− advanced breast cancer patients: A study of the Dutch SONABRE Registry

Abstract

In August 2017, cyclin‐dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy have been reimbursed in the Netherlands for patients with hormone receptor positive (HR+), HER2 negative (HER2−) advanced breast cancer (ABC). This study evaluates the implementation of CDK4/6 inhibitors and changes in treatment choices in the Netherlands. All patients diagnosed with HR+/HER2− ABC in 2009 to 2018 in seven hospitals were selected from the Southeast Netherlands Advanced Breast cancer (SONABRE) registry. The 2‐year cumulative use of CDK4/6 inhibitors since reimbursement date (August 2017) was assessed using competing‐risk methodology in two cohorts. The first cohort included patients with ABC diagnosis between August 2017 and December 2018. The second cohort included patients with ABC diagnosis between 2009 and August 2017, and still alive on August 1, 2017. In addition, treatment choices in the first three lines of therapy in calendar years 2009 to 2018 were evaluated for the total study population. Among patients diagnosed since August 2017 (n = 214), 50% (95% confidence interval [CI] = 43‐57) received CDK4/6 inhibitors within 2 years beyond diagnosis. Of eligible patients diagnosed before August 2017 (n = 417), 31% (95% CI = 27‐36) received CDK4/6 inhibitors within 2 years following reimbursement. Another 20% of both cohorts are still CDK4/6 inhibitor naïve and on first‐line therapy. The use of chemotherapy decreased in first two lines of therapy between 2009 and 2018 (first‐line: 29%‐13%; second‐line: 26%‐19%). The implementation rate of CDK4/6 inhibitors since reimbursement is currently 50% within 2 years beyond diagnosis and is expected to increase further. The implementation of targeted therapy decreased the use of chemotherapy as first‐line therapy.

Place in Therapy of Cyclin-Dependent Kinase 4/6 Inhibitors in Breast Cancer: A Targeted Literature Review

“…The study by Meegdes et al in 2021 reported on CDK4/6i treatment usage in Dutch patients with HR+/HER2− aBC based on data from the Southeast Netherlands Advanced Breast cancer (SONABRE) Registry from 2009 to 2018. This study found that since August 2017 when CDK4/6i were reimbursed in the Netherlands, CDK4/6i combined with ET was received by 31% of 214 patients in 1L, and by 44% of 71 patients in 2L with no prior exposure to CDK4/6i [ 31 ]. Additionally, CDK4/6i combined with ET usage gradually increased over time from 2014 onward in all lines reported (i.e., 1L–3L), while the use of chemotherapy, ET, and mTORi decreased [ 31 ].…”

“…This study found that since August 2017 when CDK4/6i were reimbursed in the Netherlands, CDK4/6i combined with ET was received by 31% of 214 patients in 1L, and by 44% of 71 patients in 2L with no prior exposure to CDK4/6i [ 31 ]. Additionally, CDK4/6i combined with ET usage gradually increased over time from 2014 onward in all lines reported (i.e., 1L–3L), while the use of chemotherapy, ET, and mTORi decreased [ 31 ]. An observational study by Cui et al in 2021 investigated CDK4/6i treatment usage in nearly 4000 women diagnosed with HR+/HER2− mBC in the USA between 1 January, 2013 and 31 January, 2019 based on data from the Flatiron Health database.…”

Real-world time trends in overall survival, treatments and patient characteristics in HR+/HER2− metastatic breast cancer: an observational study of the SONABRE Registry

“… 7 , 8 , 9 In a prior study of the SONABRE Registry we observed that the implementation of CDK4/6 inhibitors was somewhat lower than in other Western countries, mostly explained by the Dutch guideline recommendation that the use of CDK4/6 inhibitors in second line may be considered while awaiting the results of the SONIA study. 10 , 23 It is of importance to notice that most patients in the SONABRE Registry were treated with palbociclib as CDK4/6 inhibitor. Although no conclusions on the effectiveness of CDK4/6 inhibitors can be made from our study, our results seem to support the hypothesis that all types of CDK4/6 inhibitors may provide an overall survival benefit, despite the ongoing discussion regarding the variable significance in the phase 3 trials.…”

“…In line with guidelines, the results of the SONABRE Registry indicates that the use of everolimus is postponed to later lines of treatment since the implementation of CDK4/6 inhibitors. 10 By the introduction of PI3 kinase inhibitors in more recent years, we expect that well-chosen and more effective second- and further lines of endocrine and targeted therapies may contribute to further improvements in overall survival of patients with HR+/HER2− ABC. 24 , 25 The improved overall survival we observed in this real-world setting despite a reduced use of chemotherapy, indicates the value of endocrine and targeted therapy and fits the earlier findings of relative chemotherapy resistance in this particular breast cancer subtype.…”

“… 9 Apart from the survival outcome, prior real-world studies have shown that use of CDK4/6 inhibitors delays the use of chemotherapy. 10 , 11 Delay of chemotherapy is generally positive for patients’ quality of life, as chemotherapy usually is more toxic for patients than endocrine and targeted therapy. Accordingly, in daily practice the treatment patterns for patients diagnosed with HR+/HER2− ABC are changing.…”